dorsal/arxiv
View SchemaComplex folding pathways in a simple beta-hairpin
| Authors | Guanghong Wei, Normand Mousseau, Philippe Derreumaux |
|---|---|
| Categories | |
| ArXiv ID | q-bio/0311008 |
| URL | https://arxiv.org/abs/q-bio/0311008 |
Abstract
The determination of the folding mechanisms of proteins is critical to understand the topological change that can propagate Alzheimer and Creutzfeld-Jakobs diseases, among others. The computational community has paid considerable attention to this problem; however, the associated time scale, typically on the order of milliseconds or more, represents a formidable challenge. Ab initio protein folding from long molecular dynamics (MD) simulations or ensemble dynamics is not feasible with ordinary computing facilities and new techniques must be introduced. Here we present a detailed study of the folding of a 16-residue beta-hairpin, described by a generic energy model and using the activation-relaxation technique. From a total of 90 trajectories at 300 K, three folding pathways emerge. All involve a simultaneous optimization of the complete hydrophobic and hydrogen bonding interactions. The first two follow closely those observed by previous theoretical studies. The third pathway, never observed by previous all-atom folding, unfolding and equilibrium simulations, can be described as a reptation move of one strand of the beta-sheet with respect to the other. This reptation move indicates that non-native interactions can play a dominant role in the folding of secondary structures. These results point to a more complex folding picture than expected for a simple beta-hairpin.
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"abstract": "The determination of the folding mechanisms of proteins is critical to\nunderstand the topological change that can propagate Alzheimer and\nCreutzfeld-Jakobs diseases, among others. The computational community has paid\nconsiderable attention to this problem; however, the associated time scale,\ntypically on the order of milliseconds or more, represents a formidable\nchallenge. Ab initio protein folding from long molecular dynamics (MD)\nsimulations or ensemble dynamics is not feasible with ordinary computing\nfacilities and new techniques must be introduced. Here we present a detailed\nstudy of the folding of a 16-residue beta-hairpin, described by a generic\nenergy model and using the activation-relaxation technique. From a total of 90\ntrajectories at 300 K, three folding pathways emerge. All involve a\nsimultaneous optimization of the complete hydrophobic and hydrogen bonding\ninteractions. The first two follow closely those observed by previous\ntheoretical studies. The third pathway, never observed by previous all-atom\nfolding, unfolding and equilibrium simulations, can be described as a reptation\nmove of one strand of the beta-sheet with respect to the other. This reptation\nmove indicates that non-native interactions can play a dominant role in the\nfolding of secondary structures. These results point to a more complex folding\npicture than expected for a simple beta-hairpin.",
"arxiv_id": "q-bio/0311008",
"authors": [
"Guanghong Wei",
"Normand Mousseau",
"Philippe Derreumaux"
],
"categories": [
"q-bio.BM"
],
"title": "Complex folding pathways in a simple beta-hairpin",
"url": "https://arxiv.org/abs/q-bio/0311008"
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